Caco-2/HT29-MTX co-cultured cells as a model for studying physiological properties and toxin-induced effects on intestinal cells.
Bacterial Toxins
/ chemistry
Caco-2 Cells
Chlorides
/ metabolism
Cholera Toxin
/ chemistry
Coculture Techniques
Communicable Diseases
/ microbiology
Enterotoxins
/ chemistry
Escherichia coli
/ genetics
Escherichia coli Proteins
/ genetics
Gastrointestinal Diseases
/ microbiology
Glucose
/ metabolism
HT29 Cells
Humans
Intestinal Mucosa
/ drug effects
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2021
2021
Historique:
received:
25
02
2021
accepted:
12
09
2021
entrez:
7
10
2021
pubmed:
8
10
2021
medline:
25
11
2021
Statut:
epublish
Résumé
Infectious gastrointestinal diseases are frequently caused by toxins secreted by pathogens which may impair physiological functions of the intestines, for instance by cholera toxin or by heat-labile enterotoxin. To obtain a functional model of the human intestinal epithelium for studying toxin-induced disease mechanisms, differentiated enterocyte-like Caco-2 cells were co-cultured with goblet cell-like HT29-MTX cells. These co-cultures formed a functional epithelial barrier, as characterized by a high electrical resistance and the presence of physiological intestinal properties such as glucose transport and chloride secretion which could be demonstrated electrophysiologically and by measuring protein expression. When the tissues were exposed to cholera toxin or heat-labile enterotoxin in the Ussing chamber, cholera toxin incubation resulted in an increase in short-circuit currents, indicating an increase in apical chloride secretion. This is in line with typical cholera toxin-induced secretory diarrhea in humans, while heat-labile enterotoxin only showed an increase in short-circuit-current in Caco-2 cells. This study characterizes for the first time the simultaneous measurement of physiological properties on a functional and structural level combined with the epithelial responses to bacterial toxins. In conclusion, using this model, physiological responses of the intestine to bacterial toxins can be investigated and characterized. Therefore, this model can serve as an alternative to the use of laboratory animals for characterizing pathophysiological mechanisms of enterotoxins at the intestinal level.
Identifiants
pubmed: 34618824
doi: 10.1371/journal.pone.0257824
pii: PONE-D-21-06276
pmc: PMC8496855
doi:
Substances chimiques
Bacterial Toxins
0
Chlorides
0
Enterotoxins
0
Escherichia coli Proteins
0
Cholera Toxin
9012-63-9
Glucose
IY9XDZ35W2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0257824Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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